172732-68-2 Usage
Description
VARESPLADIB, also known as Varespladib methyl, is a small molecule inhibitor that targets the Phospholipase A2 (PLA2) enzyme family. It is a synthetic compound designed to modulate the activity of these enzymes, which play a crucial role in various cellular processes, including inflammation and cell membrane repair. VARESPLADIB has shown potential therapeutic applications in various diseases and conditions.
Uses
Used in Pharmaceutical Industry:
VARESPLADIB is used as a PLA2 inhibitor for its ability to modulate the activity of the Phospholipase A2 enzyme family, which are involved in various cellular processes such as inflammation and cell membrane repair. By inhibiting these enzymes, VARESPLADIB may help in the treatment of conditions where PLA2 activity is dysregulated.
Used in Neurodegenerative Disease Research:
VARESPLADIB is used as a secretory phospholipase A (sPLA2) inhibitor for testing its effect on human astrocytes subjected to psychosine-induced toxicity. This application aims to investigate the potential protective effects of VARESPLADIB in neurodegenerative diseases where PLA2 activity may contribute to cellular damage.
Used in Venom Research:
VARESPLADIB is used in combination with snake venom metalloproteinases (SVMP)-inhibitor, marimastat, to test its protective functionality on envenoming by vipers. This application explores the potential of VARESPLADIB in neutralizing the harmful effects of venom from certain snake species, which may have implications for the development of antivenom treatments.
Biological Activity
phospholipases (plas) produce rate-limiting precursors in the various types of biologically active lipid biosynthesis. increased levels of human nonpancreatic secretory phospholipase a2 (hnps-pla2) have been detected in several pathological conditions. ly315920 was selected for evaluation clinically as an hnps-pla2 inhibitor.
Biochem/physiol Actions
Varespladib is effective against viper and elapid venoms and is used in snakebite therapy. It is reported to interact with the hydrophobic channel of the PLA2-like toxin in in vitro structural studies. It blocks inflammatory cascades related to the sPLA2.
in vitro
the true potency of ly315920 was defined to be a mole fraction of 1.5 x 10-6 using a deoxycholate/phosphatidylcholine assay. ly315920 was found to be 40-fold less active against human, group ib, pancreatic spla2 and was inactive against cytosolic pla2 and the constitutive and inducible forms of cyclooxygenase. human spla2-induced thromboxane a2 release from isolated guinea pig lung bronchoalveolar lavage cells was inhibited by ly315920 with the ic50 of 0.79 μm [1].
in vivo
the i.v. administration of ly315920, 5 min before the bronchoalveolar lavage cells harvest, led to the inhibition of spla2-induced production of txa2 with an ed50 of 16.1 mg/kg. [2].
IC 50
9 ± 1 nm or 7.3 x 10-6 mole fraction for spla2 activity
references
[1] snyder dw, bach nj, dillard rd, draheim se, carlson dg, fox n, roehm nw, armstrong ct, chang ch, hartley lw, johnson lm, roman cr, smith ac, song m, fleisch jh. pharmacology of ly315920/s-5920, [[3-(aminooxoacetyl)-2-ethyl-1- (phenylmethyl)-1h-indol-4-yl]oxy] acetate, a potent and selective secretory phospholipase a2 inhibitor: a new class of anti-inflammatory drugs, spi. j pharmacol exp ther. 1999;288(3):1117-24.[2] rosenson rs, hislop c, elliott m, stasiv y, goulder m, waters d. effects of varespladib methyl on biomarkers and major cardiovascular events in acute coronary syndrome patients. j am coll cardiol. 2010;56(14):1079-88.
Check Digit Verification of cas no
The CAS Registry Mumber 172732-68-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,7,2,7,3 and 2 respectively; the second part has 2 digits, 6 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 172732-68:
(8*1)+(7*7)+(6*2)+(5*7)+(4*3)+(3*2)+(2*6)+(1*8)=142
142 % 10 = 2
So 172732-68-2 is a valid CAS Registry Number.
InChI:InChI=1/C21H20N2O5.Na/c1-2-14-19(20(26)21(22)27)18-15(9-6-10-16(18)28-12-17(24)25)23(14)11-13-7-4-3-5-8-13;/h3-10H,2,11-12H2,1H3,(H2,22,27)(H,24,25);/q;+1/p-1
172732-68-2Relevant articles and documents
Regioselective synthesis of 4- and 7-alkoxyindoles from 2,3-dihalophenols: Application to the preparation of indole inhibitors of phospholipase A 2
Sanz, Roberto,Castroviejo, M. Pilar,Guilarte, Veronica,Perez, Antonio,Fananas, Francisco J.
, p. 5113 - 5118 (2008/02/05)
(Chemical Equation Presented) An efficient and regioselective synthesis of 4- and 7-alkoxyindoles has been developed from commercially available starting materials such as 3-halophenols and 3-chloroanisole. Directed ortho-metalation followed by two pallad
Method for treating sepsis
-
, (2008/06/13)
A novel method of treating and/or preventing sepsis.
METHOD FOR TRATMENT OF NON-RHEUMATOID ARTHRITIS
-
, (2008/06/13)
A method is disclosed for the treatment of non-rheumatoid arthritis by administering to a mammal in need thereof a therapeutically effective amount of an sPLA 2 inhibitor.
